TY - JOUR
T1 - Preliminary results on safety and activity of a randomized, double-blind, 2 X 2 trial of low-dose tamoxifen and fenretinide for breast cancer prevention in premenopausal women
AU - Guerrieri-Gonzaga, Aliana
AU - Robertson, Chris
AU - Bonanni, Bernardo
AU - Serrano, Davide
AU - Cazzaniga, Massimiliano
AU - Mora, Serena
AU - Gulisano, Marcella
AU - Johansson, Harriet
AU - Intra, Mattia
AU - Latronico, Antuono
AU - Franchi, Dorella
AU - Pelosi, Giuseppe
AU - Johnson, Karen
AU - Decensi, Andrea
PY - 2006/1/1
Y1 - 2006/1/1
N2 - Purpose: To determine whether low-dose tamoxifen and fenretinide have a synergistic effect on surrogate biomarkers, including circulating insulin-like growth factor I (IGF-I) and mammographic density, in premenopausal women at risk for breast cancer and to study drug safety. Patients and Methods: Premenopausal women (n = 235) were randomly assigned in a double-blind four-arm trial to receive tamoxifen 5 mg/d, fenretinide 200 mg/d, both agents, or placebo for 2 years. The present analysis refers to preliminary data on safety, IGF-I, and breast cancer events. Results: Patients were included if they had an excised ductal carcinoma-in-situ (57%), lobular carcinoma-in-situ (13%), minimal invasive breast cancer (7%), or a 5-year Gail risk ≥ 1.3% (23%). After a median follow-up of 40 months, there was a reduction of 13%, 2%, 20%, and 1 % in IGF-I levels for patients on tamoxifen, fenretinide, tamoxifen plus fenretinide, and placebo, respectively. Recruitment was stopped based on the lack of an interaction on IGF-I levels, which was a primary end point for the study. Thirty-six patients have dropped out of the study, 17 because of adverse events and 19 for various other reasons. One stage I endometrial cancer occurred in a patient on fenretinide, and one optic nerve ischemia and one deep venous thrombosis occurred on tamoxifen. There was no difference in menopausal symptoms, endometrial thickness, polyps, or ovarian cysts among treatment arms. To date, 24 breast cancers have been observed, without differences among arms. Conclusion: The combination of low-dose tamoxifen and fenretinide is safe but not synergistic in lowering IGF-I levels in premenopausal women. The clinical implications require further follow-up.
AB - Purpose: To determine whether low-dose tamoxifen and fenretinide have a synergistic effect on surrogate biomarkers, including circulating insulin-like growth factor I (IGF-I) and mammographic density, in premenopausal women at risk for breast cancer and to study drug safety. Patients and Methods: Premenopausal women (n = 235) were randomly assigned in a double-blind four-arm trial to receive tamoxifen 5 mg/d, fenretinide 200 mg/d, both agents, or placebo for 2 years. The present analysis refers to preliminary data on safety, IGF-I, and breast cancer events. Results: Patients were included if they had an excised ductal carcinoma-in-situ (57%), lobular carcinoma-in-situ (13%), minimal invasive breast cancer (7%), or a 5-year Gail risk ≥ 1.3% (23%). After a median follow-up of 40 months, there was a reduction of 13%, 2%, 20%, and 1 % in IGF-I levels for patients on tamoxifen, fenretinide, tamoxifen plus fenretinide, and placebo, respectively. Recruitment was stopped based on the lack of an interaction on IGF-I levels, which was a primary end point for the study. Thirty-six patients have dropped out of the study, 17 because of adverse events and 19 for various other reasons. One stage I endometrial cancer occurred in a patient on fenretinide, and one optic nerve ischemia and one deep venous thrombosis occurred on tamoxifen. There was no difference in menopausal symptoms, endometrial thickness, polyps, or ovarian cysts among treatment arms. To date, 24 breast cancers have been observed, without differences among arms. Conclusion: The combination of low-dose tamoxifen and fenretinide is safe but not synergistic in lowering IGF-I levels in premenopausal women. The clinical implications require further follow-up.
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U2 - 10.1200/JCO.2005.02.9934
DO - 10.1200/JCO.2005.02.9934
M3 - Article
C2 - 16382122
AN - SCOPUS:33644839534
VL - 24
SP - 129
EP - 135
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 1
ER -